314 research outputs found

    Molecular Psychiatry

    No full text
    The book highlights important aspects of Molecular Psychiatry, including molecular mechanisms, animal models, biomarkers, advanced methods, drugs and antidepressant response, as well as genetics and epigenetics. Molecular mechanisms are a vital part of the search for the biological basis of psychiatric disorders, providing molecular hints that can later be tested as biomarkers or targets for drug development. Animal models represent a commonly used approach to aid in this bench-to-bed translation; the examples here are social defeat stress and the Roman High-Avoidance (RHA) and the Roman Low-Avoidance (RLA) rats. For biomarkers, psychiatric disorders pose a particular challenge due to the tissue specificity of many currently investigated biomarkers; i.e., not all blood-based measures directly represent changes in the brain. The Ebook includes five articles focused on the challenges of identifying clinically and biologically relevant biomarkers for psychiatric disorders. Scientific progress typically is fostered by the development of new methods. The application of machine learning methods for the proper analysis of Big Data and induced pluripotent stem cells are examples outlined in this Ebook. Furthermore, three articles are devoted to the understanding of the mechanisms of actions of existing drugs with the ultimate goal of identifying ways to predict treatment response in patients. Finally, three articles deepen the insight into the genetics and epigenetics of psychiatric disorders

    Jakob Friedrich Fries (1773-1843): Eine Philosophie der exakten Wissenschaften

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    Jakob Friedrich Fries (1773-1843): A Philosophy of the Exact Sciences -/- Shortened version of the article of the same name in: Tabula Rasa. Jenenser magazine for critical thinking. 6th of November 1994 edition -/- 1. Biography -/- Jakob Friedrich Fries was born on the 23rd of August, 1773 in Barby on the Elbe. Because Fries' father had little time, on account of his journeying, he gave up both his sons, of whom Jakob Friedrich was the elder, to the Herrnhut Teaching Institution in Niesky in 1778. Fries attended the theological seminar in Niesky in autumn 1792, which lasted for three years. There he (secretly) began to study Kant. The reading of Kant's works led Fries, for the first time, to a deep philosophical satisfaction. His enthusiasm for Kant is to be understood against the background that a considerable measure of Kant's philosophy is based on a firm foundation of what happens in an analogous and similar manner in mathematics. -/- During this period he also read Heinrich Jacobi's novels, as well as works of the awakening classic German literature; in particular Friedrich Schiller's works. In 1795, Fries arrived at Leipzig University to study law. During his time in Leipzig he became acquainted with Fichte's philosophy. In autumn of the same year he moved to Jena to hear Fichte at first hand, but was soon disappointed. -/- During his first sojourn in Jenaer (1796), Fries got to know the chemist A. N. Scherer who was very influenced by the work of the chemist A. L. Lavoisier. Fries discovered, at Scherer's suggestion, the law of stoichiometric composition. Because he felt that his work still need some time before completion, he withdrew as a private tutor to Zofingen (in Switzerland). There Fries worked on his main critical work, and studied Newton's "Philosophiae naturalis principia mathematica". He remained a lifelong admirer of Newton, whom he praised as a perfectionist of astronomy. Fries saw the final aim of his mathematical natural philosophy in the union of Newton's Principia with Kant's philosophy. -/- With the aim of qualifying as a lecturer, he returned to Jena in 1800. Now Fries was known from his independent writings, such as "Reinhold, Fichte and Schelling" (1st edition in 1803), and "Systems of Philosophy as an Evident Science" (1804). The relationship between G. W. F. Hegel and Fries did not develop favourably. Hegel speaks of "the leader of the superficial army", and at other places he expresses: "he is an extremely narrow-minded bragger". On the other hand, Fries also has an unfavourable take on Hegel. He writes of the "Redundancy of the Hegelistic dialectic" (1828). In his History of Philosophy (1837/40) he writes of Hegel, amongst other things: "Your way of philosophising seems just to give expression to nonsense in the shortest possible way". In this work, Fries appears to argue with Hegel in an objective manner, and expresses a positive attitude to his work. -/- In 1805, Fries was appointed professor for philosophy in Heidelberg. In his time spent in Heidelberg, he married Caroline Erdmann. He also sealed his friendships with W. M. L. de Wette and F. H. Jacobi. Jacobi was amongst the contemporaries who most impressed Fries during this period. In Heidelberg, Fries wrote, amongst other things, his three-volume main work New Critique of Reason (1807). -/- In 1816 Fries returned to Jena. When in 1817 the Wartburg festival took place, Fries was among the guests, and made a small speech. 1819 was the so-called "Great Year" for Fries: His wife Caroline died, and Karl Sand, a member of a student fraternity, and one of Fries' former students stabbed the author August von Kotzebue to death. Fries was punished with a philosophy teaching ban but still received a professorship for physics and mathematics. Only after a period of years, and under restrictions, he was again allowed to read philosophy. From now on, Fries was excluded from political influence. The rest of his life he devoted himself once again to philosophical and natural studies. During this period, he wrote "Mathematical Natural Philosophy" (1822) and the "History of Philosophy" (1837/40). -/- Fries suffered from a stroke on New Year's Day 1843, and a second stroke, on the 10th of August 1843 ended his life. -/- 2. Fries' Work Fries left an extensive body of work. A look at the subject areas he worked on makes us aware of the universality of his thinking. Amongst these subjects are: Psychic anthropology, psychology, pure philosophy, logic, metaphysics, ethics, politics, religious philosophy, aesthetics, natural philosophy, mathematics, physics and medical subjects, to which, e.g., the text "Regarding the optical centre in the eye together with general remarks about the theory of seeing" (1839) bear witness. With popular philosophical writings like the novel "Julius and Evagoras" (1822), or the arabesque "Longing, and a Trip to the Middle of Nowhere" (1820), he tried to make his philosophy accessible to a broader public. Anthropological considerations are shown in the methodical basis of his philosophy, and to this end, he provides the following didactic instruction for the study of his work: "If somebody wishes to study philosophy on the basis of this guide, I would recommend that after studying natural philosophy, a strict study of logic should follow in order to peruse metaphysics and its applied teachings more rapidly, followed by a strict study of criticism, followed once again by a return to an even closer study of metaphysics and its applied teachings." -/- 3. Continuation of Fries' work through the Friesian School -/- Fries' ideas found general acceptance amongst scientists and mathematicians. A large part of the followers of the "Fries School of Thought" had a scientific or mathematical background. Amongst them were biologist Matthias Jakob Schleiden, mathematics and science specialist philosopher Ernst Friedrich Apelt, the zoologist Oscar Schmidt, and the mathematician Oscar Xavier Schlömilch. Between the years 1847 and 1849, the treatises of the "Fries School of Thought", with which the publishers aimed to pursue philosophy according to the model of the natural sciences appeared. In the Kant-Fries philosophy, they saw the realisation of this ideal. The history of the "New Fries School of Thought" began in 1903. It was in this year that the philosopher Leonard Nelson gathered together a small discussion circle in Goettingen. Amongst the founding members of this circle were: A. Rüstow, C. Brinkmann and H. Goesch. In 1904 L. Nelson, A. Rüstow, H. Goesch and the student W. Mecklenburg travelled to Thuringia to find the missing Fries writings. In the same year, G. Hessenberg, K. Kaiser and Nelson published the first pamphlet from their first volume of the "Treatises of the Fries School of Thought, New Edition". -/- The school set out with the aim of searching for the missing Fries' texts, and re-publishing them with a view to re-opening discussion of Fries' brand of philosophy. The members of the circle met regularly for discussions. Additionally, larger conferences took place, mostly during the holidays. Featuring as speakers were: Otto Apelt, Otto Berg, Paul Bernays, G. Fraenkel, K. Grelling, G. Hessenberg, A. Kronfeld, O. Meyerhof, L. Nelson and R. Otto. On the 1st of March 1913, the Jakob-Friedrich-Fries society was founded. Whilst the Fries' school of thought dealt in continuum with the advancement of the Kant-Fries philosophy, the members of the Jakob-Friedrich-Fries society's main task was the dissemination of the Fries' school publications. In May/June, 1914, the organisations took part in their last common conference before the gulf created by the outbreak of the First World War. Several members died during the war. Others returned disabled. The next conference took place in 1919. A second conference followed in 1921. Nevertheless, such intensive work as had been undertaken between 1903 and 1914 was no longer possible. -/- Leonard Nelson died in October 1927. In the 1930's, the 6th and final volume of "Treatises of the Fries School of Thought, New Edition" was published. Franz Oppenheimer, Otto Meyerhof, Minna Specht and Grete Hermann were involved in their publication. -/- 4. About Mathematical Natural Philosophy -/- In 1822, Fries' "Mathematical Natural Philosophy" appeared. Fries rejects the speculative natural philosophy of his time - above all Schelling's natural philosophy. A natural study, founded on speculative philosophy, ceases with its collection, arrangement and order of well-known facts. Only a mathematical natural philosophy can deliver the necessary explanatory reasoning. The basic dictum of his mathematical natural philosophy is: "All natural theories must be definable using purely mathematically determinable reasons of explanation." Fries is of the opinion that science can attain completeness only by the subordination of the empirical facts to the metaphysical categories and mathematical laws. -/- The crux of Fries' natural philosophy is the thought that mathematics must be made fertile for use by the natural sciences. However, pure mathematics displays solely empty abstraction. To be able to apply them to the sensory world, an intermediatory connection is required. Mathematics must be connected to metaphysics. The pure mechanics, consisting of three parts are these: a) A study of geometrical movement, which considers solely the direction of the movement, b) A study of kinematics, which considers velocity in Addition, c) A study of dynamic movement, which also incorporates mass and power, as well as direction and velocity. -/- Of great interest is Fries' natural philosophy in view of its methodology, particularly with regard to the doctrine "leading maxims". Fries calls these "leading maxims" "heuristic", "because they are principal rules for scientific invention". -/- Fries' philosophy found great recognition with Carl Friedrich Gauss, amongst others. Fries asked for Gauss's opinion on his work "An Attempt at a Criticism based on the Principles of the Probability Calculus" (1842). Gauss also provided his opinions on "Mathematical Natural Philosophy" (1822) and on Fries' "History of Philosophy". Gauss acknowledged Fries' philosophy and wrote in a letter to Fries: "I have always had a great predilection for philosophical speculation, and now I am all the more happy to have a reliable teacher in you in the study of the destinies of science, from the most ancient up to the latest times, as I have not always found the desired satisfaction in my own reading of the writings of some of the philosophers. In particular, the writings of several famous (maybe better, so-called famous) philosophers who have appeared since Kant have reminded me of the sieve of a goat-milker, or to use a modern image instead of an old-fashioned one, of Münchhausen's plait, with which he pulled himself from out of the water. These amateurs would not dare make such a confession before their Masters; it would not happen were they were to consider the case upon its merits. I have often regretted not living in your locality, so as to be able to glean much pleasurable entertainment from philosophical verbal discourse." -/- The starting point of the new adoption of Fries was Nelson's article "The critical method and the relation of psychology to philosophy" (1904). Nelson dedicates special attention to Fries' re-interpretation of Kant's deduction concept. Fries awards Kant's criticism the rationale of anthropological idiom, in that he is guided by the idea that one can examine in a psychological way which knowledge we have "a priori", and how this is created, so that we can therefore recognise our own knowledge "a priori" in an empirical way. Fries understands deduction to mean an "awareness residing darkly in us is, and only open to basic metaphysical principles through conscious reflection.". -/- Nelson has pointed to an analogy between Fries' deduction and modern metamathematics. In the same manner, as with the anthropological deduction of the content of the critical investigation into the metaphysical object show, the content of mathematics become, in David Hilbert's view, the object of metamathematics. -/

    Molecular Psychiatry

    No full text
    The book highlights important aspects of Molecular Psychiatry, including molecular mechanisms, animal models, biomarkers, advanced methods, drugs and antidepressant response, as well as genetics and epigenetics. Molecular mechanisms are a vital part of the search for the biological basis of psychiatric disorders, providing molecular hints that can later be tested as biomarkers or targets for drug development. Animal models represent a commonly used approach to aid in this bench-to-bed translation; the examples here are social defeat stress and the Roman High-Avoidance (RHA) and the Roman Low-Avoidance (RLA) rats. For biomarkers, psychiatric disorders pose a particular challenge due to the tissue specificity of many currently investigated biomarkers; i.e., not all blood-based measures directly represent changes in the brain. The Ebook includes five articles focused on the challenges of identifying clinically and biologically relevant biomarkers for psychiatric disorders. Scientific progress typically is fostered by the development of new methods. The application of machine learning methods for the proper analysis of Big Data and induced pluripotent stem cells are examples outlined in this Ebook. Furthermore, three articles are devoted to the understanding of the mechanisms of actions of existing drugs with the ultimate goal of identifying ways to predict treatment response in patients. Finally, three articles deepen the insight into the genetics and epigenetics of psychiatric disorders

    Hyperpolarization of 15N‐Pyridinium by Using Parahydrogen Enables Access to Reactive Oxygen Sensors and Pilot In Vivo Studies

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    Magnetic resonance with hyperpolarized contrast agents is one of the most powerful and noninvasive imaging platforms capable for investigating in vivo metabolism. While most of the utilized hyperpolarized agents are based on 13C nuclei, a milestone advance in this area is the emergence of 15N hyperpolarized contrast agents. Currently, the reported 15N hyperpolarized agents mainly utilize the dissolution dynamic nuclear polarization (d‐DNP) protocol. The parahydrogen enhanced 15N probes have proven to be elusive and have been tested almost exclusively in organic solvents. Herein, we designed a reaction based reactive oxygen sensor 15N‐boronobenzyl‐2‐styrylpyridinium (15N‐BBSP) which can be hyperpolarized with para‐hydrogen. Reactive oxygen species plays a vital role as one of the essential intracellular signalling molecules. Disturbance of the H2O2 level usually represents a hallmark of pathophysiological conditions. This H2O2 probe exhibited rapid responsiveness toward H2O2 and offered spectrally resolvable chemical shifts. We also provide strategies to bring the newly developed probe from the organic reaction solution into a biocompatible injection buffer and demonstrate the feasibility of in vivo 15N signal detection. The present work manifests its great potential not only for reaction based reactive sensing probes but also promises to serve as a platform to develop other contrast agents

    Pressure Frying of French Fries

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    This Dissertation / Report is the outcome of investigation carried out by the creator(s) / author(s) at the department/division of Central Food Technological Research Institute (CFTRI), Mysore mentioned below in this page

    Characterization and application of a coating of starch extracted from avocado (Persea americana L. cv. Hass) seeds as an alternative to reduce acrylamide content in French fries

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    The starch extracted from avocado (Persea americana L. cv. Hass) seeds was characterized and used in the preparation of an edible coating to reduce the oil uptake and acrylamide content in French fries. Starch characterization was carried out using Differential Scanning Calorimetry, Fourier transform infrared spectrophotometry, gelatinization, and scanning electron microscopy. Uncoated (UFF) and coated (CFF) French fries were compared and evaluated for moisture, water activity (Aw), fat, color, firmness, acrylamide content, and sensorial analysis. The extracted starch presented a high crystalline structure and good stability to mechanical work and heat treatments. The CFF French fries showed significantly higher Aw, color parameter a*, but lower luminosity and acrylamide content than UFF samples. Similarly, the CFF samples tended to decrease the fat content, although without statistical differences. Avocado seed starch can be an economical and technically feasible alternative to the food industry as an effective coating to reduce acrylamide content in French fries.The authors are grateful for the financial support provided by Universidad de Antioquia. The authors gratefully acknowledge the Laboratories of BIOALI and Sensory Analysis of the Universidad de Antioquia. The author Oscar Vega-Castro gratefully acknowledges the Corporación Universitaria Americana for the financial support of the research project. The authors are grateful to the company Poltec S.A.S (La Estrella, Medellín, Colombia).Open Access funding provided by Colombia Consortium.Peer reviewe

    La geometria eterna. Nelson e le geometrie non-euclidee

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    The “discovery” of non-Euclidean geometries had profound repercussions on the sciences and philosophy alike and opened a heated debate on the nature of space and on the origin of geometry and its axioms. At the heart of the discussion lay Kant’s doctrine of space. Nelson took part in this debate, rejecting the three main theories of time: the logical, the empirical and the conventionalist. Referring to J. F. Fries’ philosophy, he tried to demonstrate the a priori, synthetic nature of Euclidean axioms and the merely logical character of non-Euclidean geometries. His attempt, though interesting, ended according to the Author of this essay in failure. Keywords: Non-Euclidean geometries, logical interpretation, empiricism, conventionalism, ontological relativity, functionalism, L. Nelso

    Parahydrogen-enhanced pH measurements using [1- 13 C]bicarbonate derived from non-enzymatic decarboxylation of [1- 13 C]pyruvate-d 3

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    PHIP and non-enzymatic decarboxylation of [1- 13 C]pyruvate-d 3 were applied to obtain, in less than one minute, [1- 13 C]bicarbonate, an accurate and biocompatible pH sensor. This probe is suitable for future in vivo studies of acid-base imbalances.Alterations in pH are a hallmark in several pathologies including cancer, ischemia, and inflammation. Non-invasive magnetic resonance methods to measure pH offer a new approach for early diagnosis of diseases characterized by acid–base imbalances. The hyperpolarization with parahydrogen-induced polarization (PHIP) enhances inherently low signals in magnetic resonance experiments by several orders of magnitude and offers a suitable platform to obtain biocompatible markers in less than one minute. Here, we present an optimized preparation of an hyperpolarized H 13 CO 3 − / 13 CO 2 pH sensor via non-enzymatic decarboxylation with H 2 O 2 of [1- 13 C]pyruvate-d 3 obtained by PHIP at 7 T. An improved 13 C polarization of purified [1- 13 C]pyruvate-d 3 in water with 36.65 ± 0.06% polarization was obtained starting from 50 mM precursor. Subsequent decarboxylation, H 13 CO 3 − / 13 CO 2 exhibited 12.46 ± 0.01% of polarization at physiological pH, 45 seconds after the reaction start. Considering the dilution factor that [1- 13 C]pyruvate-d 3 exhibits in vivo , we optimized our methodology to test the accuracy of the pH sensor at single digit millimolar concentration. In vitro pH estimations on phantoms and cell culture media demonstrated accurate pH calculations with uncertainties of less than 0.08 units. These promising results highlight the efficiency of a pH sensor generated via PHIP in less than one minute, with remarkable polarization, and biocompatibility suitable for future in vivo studies.PHIP and non-enzymatic decarboxylation of [1- 13 C]pyruvate-d 3 were applied to obtain, in less than one minute, [1- 13 C]bicarbonate, an accurate and biocompatible pH sensor. This probe is suitable for future in vivo studies of acid-base imbalances.Alterations in pH are a hallmark in several pathologies including cancer, ischemia, and inflammation. Non-invasive magnetic resonance methods to measure pH offer a new approach for early diagnosis of diseases characterized by acid–base imbalances. The hyperpolarization with parahydrogen-induced polarization (PHIP) enhances inherently low signals in magnetic resonance experiments by several orders of magnitude and offers a suitable platform to obtain biocompatible markers in less than one minute. Here, we present an optimized preparation of an hyperpolarized H 13 CO 3 − / 13 CO 2 pH sensor via non-enzymatic decarboxylation with H 2 O 2 of [1- 13 C]pyruvate-d 3 obtained by PHIP at 7 T. An improved 13 C polarization of purified [1- 13 C]pyruvate-d 3 in water with 36.65 ± 0.06% polarization was obtained starting from 50 mM precursor. Subsequent decarboxylation, H 13 CO 3 − / 13 CO 2 exhibited 12.46 ± 0.01% of polarization at physiological pH, 45 seconds after the reaction start. Considering the dilution factor that [1- 13 C]pyruvate-d 3 exhibits in vivo , we optimized our methodology to test the accuracy of the pH sensor at single digit millimolar concentration. In vitro pH estimations on phantoms and cell culture media demonstrated accurate pH calculations with uncertainties of less than 0.08 units. These promising results highlight the efficiency of a pH sensor generated via PHIP in less than one minute, with remarkable polarization, and biocompatibility suitable for future in vivo studies.H2020 European Research Council https://doi.org/10.13039/100010663Max-Planck-Gesellschaft https://doi.org/10.13039/501100004189Deutsche Forschungsgemeinschaft https://doi.org/10.13039/50110000165

    Pharmacoepigenetics of Bipolar Disorder

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